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Henry I. Mosberg
Associate Dean for Research and Graduate Education
Tom D. Rowe Collegiate Professor of Medicinal Chemistry

College of Pharmacy Faculty
UofM Directory
Phone: (734)764-8117
Physical Chemistry, University of Illinois, Urbana-Champaign (1977)

Research Interests

Design and synthesis of opioid peptide and peptidomimetic ligands

G protein-coupled receptor structure and function

Modeling of membrane proteins

Elucidation of ligand-receptor interactions

Selected Publications

Harland A.A., Bender A.M., Griggs N.W., Gao C., Anand J.P., Pogozheva I.D., Traynor J.R., Jutkiewicz E.M., Mosberg H.I.
Effects of N-substitutions on the tetrahydroquinoline (THQ) core of mixed-efficacy mu-opioid receptor (MOR)/delta-opioid receptor (DOR) ligands
J Med Chem, 59: 4985-4998 (2016)


Anand J.P., Boyer B.T., Mosberg H.I., Jutkiewicz E.M.
The behavioral effects of a mixed efficacy antinociceptive peptide, VRP26, following chronic administration in mice
Psychopharmacology (Berl), 233: 2479-2487 (2016)


Harland A.A., Yeomans L., Griggs N.W., Anand J.P., Pogozheva I.D., Jutkiewicz E.M., Traynor J.R., Mosberg H.I.
Further optimization and evaluation of bioavailable, mixed-efficacy mu-opioid receptor (MOR) agonists/delta-opioid receptor (DOR) antagonists: balancing MOR and DOR affinities
J Med Chem, 58: 8952-8969 (2015)


Geng J., Pogozheva I.D., Mosberg H.I., Raghavan M.
Use of functional polymorphisms to elucidate the peptide binding site of TAP complexes
J Immunol, 196: pii: 1500985 (2015)


Kumar V., Ridzwan I.E., Grivas K., Lewis J.W., Clark M.J., Meurice C., Jimenez-Gomez C., Pogozheva I., Mosberg H., Traynor J.R., Husbands S.M.
Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity
J Med Chem, 57: 4049-4057 (2014)


Bender A.M., Griggs N.W., Anand J.P., Traynor J.R., Jutkiewicz E.M., Mosberg H.I.
Asymmetric synthesis and in vitro and in vivo activity of tetrahydroquinolines featuring a diverse set of polar substitutions at the 6 position as mixed-efficacy mu opioid receptor/delta opioid receptor ligands
ACS Chem Neurosci, 6: 1428-1435 (2014)


Pogozheva I.D., Mosberg H.I., Lomize A.L.
Life at the border: adaptation of proteins to anisotropic membrane environment
Protein Sci, 23: 1165-1196 (2014)


Mosberg H.I., Yeomans L., Anand J.P., Porter V., Sobczyk-Kojiro K., Traynor J.R., Jutkiewicz E.M.
Development of a bioavailable mu opioid receptor (MOPr) agonist, delta opioid receptor (DOPr) antagonist peptide that evokes antinociception without development of acute tolerance
J Med Chem, 57: 3148-3153 (2014)


Anand J.P., Porter-Barrus V.R., Waldschmidt H.V., Yeomans L., Pogozheva I.D., Traynor J.R., Mosberg H.I.
Translation of structure-activity relationships from cyclic mixed efficacy opioid peptides to linear analogues
Biopolymers, 102: 107-114 (2014)


Ding B., Glukhova A., Sobczyk-Kojiro K., Mosberg H.I., Tesmer J.J., Chen Z.
Unveiling the membrane-binding properties of N-terminal and C-terminal regions of G protein-coupled receptor kinase 5 by combined optical spectroscopies
Langmuir, 30: 823-831 (2014)


Bender A.M., Clark M.J., Agius M.P., Traynor J.R., Mosberg H.I.
Synthesis and evaluation of 4-substituted piperidines and piperazines as balanced affinity mu opioid receptor (MOR) agonist/delta opioid receptor (DOR) antagonist ligands
Bioorg Med Chem Lett, 24: 548-551 (2014)


Pogozheva I.D., Tristram-Nagle S., Mosberg H.I., Lomize A.L.
Structural adaptations of proteins to different biological membranes
Biochim Biophys Acta-Biomembranes, 1828: 2592-2608 (2013)


Mosberg H.I., Yeomans L., Harland A.A., Bender A.M., Sobczyk-Kojiro K., Anand J.P., Clark M.J., Jutkiewicz E.M., Traynor J.R.
Opioid peptidomimetics: leads for the design of bioavailable mixed efficacy mu opioid receptor (MOR) agonist/delta opioid receptor (DOR) antagonist ligands
J Med Chem, 56: 2139-2149 (2013)


Anand J.P., Purington L.C., Pogozheva I.D., Traynor J.R., Mosberg H.I.
Modulation of opioid receptor ligand affinity and efficacy using active and inactive state receptor models
Chem Biol Drug Des, 80: 763-770 (2012)


Janovick J.A., Pogozheva I.D., Mosberg H.I., Cornea A., Conn P.M.
Rescue of misrouted GnRHR Mutants reveals its constitutive activity
Mol Endocrinol, 26: 1179-1188 (2012)


Lomize M.A., Pogozheva I.D., Joo H., Mosberg H.I., Lomize A.L.
OPM database and PPM web server: resources for positioning of proteins in membranes
Nucleic Acids Res, 40(Database issue): D370-D376 (2012)


Purington L.C., Sobczyk-Kojiro K., Pogozheva I.D., Traynor J.R., Mosberg H.I.
Development and in vitro characterization of a novel bifunctional mu-agonist/delta-antagonist opioid tetrapeptide
ACS Chem Biol, 6: 1375-1381 (2011)


Girnys E.A., Porter V.R., Mosberg H.I.
Conformationally restricted analogs of the direct thrombin inhibitor FM 19
Bioorg Med Chem, 19: 7425-7434 (2011)


Lomize AL, Pogozheva ID, Mosberg HI.
Anisotropic solvent model of the lipid bilayer. 2. Energetics of insertion of small molecules, peptides, and proteins in membranes.
J Chem Inf Model, 51: 930-946 (2011)


Lomize AL, Pogozheva ID, Mosberg HI.
Anisotropic solvent model of the lipid bilayer. 1. Parameterization of long-range electrostatics and first solvation shell effects.
J Chem Inf Model, 51: 918-929 (2011)


Janovick JA, Pogozheva ID, Mosberg HI, Conn PM.
Salt bridges overlapping the gonadotropin-releasing hormone receptor agonist binding site reveal a coincidence detector for g protein-coupled receptor activation.
J Pharmacol Exp Ther, 338: 430-442 (2011)


René P, Le Gouill C, Pogozheva ID, Lee G, Mosberg HI, Farooqi IS, Valenzano KJ, Bouvier M.
Pharmacological chaperones restore function to MC4R mutants responsible for severe early-onset obesity.
J Pharmacol Exp Ther, 335: 520-532 (2010)


Girnys EA, Sobczyk-Kojiro K, Mosberg HI.
Structure-based design of residue 1 analogs of the direct thrombin inhibitor pentapeptide FM 19.
Chem Biol Drug Des, 75(1): 35-39 (2010)


Tan K, Pogozheva ID, Yeo GS, Hadaschik D, Keogh JM, Haskell-Leuvano C, O Rahilly S, Mosberg HI, Farooqi IS.
Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor.
Endocrinology, 150(1): 114-125 (2009)


Kuszak AJ, Pitchiaya S, Anand JP, Mosberg HI, Walter NG, Sunahara RK.
Purification and functional reconstitution of monomeric mu-opioid receptors: allosteric modulation of agonist binding by Gi2.
J Biol Chem, 284(39): 26732-26741 (2009)


Roof RA, Roman DL, Clements ST, Sobczyk-Kojiro K, Blazer LL, Ota S, Mosberg HI, Neubig RR.
A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen.
BMC Pharmacol., 9: 9 (2009)


Roof RA, Sobczyk-Kojiro K, Turbiak AJ, Roman DL, Pogozheva ID, Blazer LL, Neubig RR, Mosberg HI.
Novel peptide ligands of RGS4 from a focused one-bead, one-compound library.
Chem Biol Drug Des, 72(2): 111-119 (2008)


Proneth B, Pogozheva ID, Portillo FP, Mosberg HI, Haskell-Luevano C.
Melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 modified at the para position of the benzyl side chain (DPhe): importance for mouse melanocortin-3 receptor agonist versus antagonist activity.
J Med Chem, 51(18): 5585-5593 (2008)


Nieman MT, Burke F, Warnock M, Zhou Y, Sweigart J, Chen A, Ricketts D, Lucchesi BR, Chen Z, Di Cera E, Hilfinger J, Kim JS, Mosberg HI, Schmaier AH.
Thrombostatin FM compounds: direct thrombin inhibitors - mechanism of action in vitro and in vivo
J Thromb Haemost, 6(5): 837-845 (2008)


Lomize AL, Pogozheva ID, Lomize MA, Mosberg HI
The role of hydrophobic interactions in positioning of peripheral proteins in membranes
BMC Struct Biol, 7: 44 (2007)


Xiang Z, Pogozheva ID, Sorenson NB, Wilczynski AM, Holder JR, Litherland SA, Millard WJ, Mosberg HI, Haskell-Luevano C.
Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms
Biochemistry, 46(28): 8273-8287 (2007)


Lomize AL, Pogozheva ID, Lomize MA, Mosberg HI
Positioning of proteins in membranes: a computational approach
Protein Sci., 15: 1318-1333 (2006)


Burke FM, Warnock M, Schmaier AH, Mosberg HI
Synthesis of novel peptide inhibitors of thrombin-induced platelet activation
Chem. Biol. Drug. Des., 68: 235-258 (2006)


Roof RA, Jin Y, Roman DL, Sunahara RK, Ishii M, Mosberg HI, Neubig RR
Mechanism of Action and Structural Requirements of Constrained Peptide Inhibitors of RGS Proteins
Chem. Biol. Drug. Des., 67: 266-274 (2006)


Torregrossa MM, Jutkiewicz EM, Mosberg HI, Balboni G, Watson SJ, Woods JH
Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats.
Brain Res., 1069: 172-181 (2006)


Jutkiewicz EM, Torregrossa MM, Sobczyk-Kojiro K, Mosberg HI, Folk JE, Rice KC, Watson SJ, Woods JH
Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects.
Eur J Pharmacol., 531: 151-159 (2006)


Lomize MA, Lomize AL, Pogozheva ID, Mosberg HI
OPM: orientations of proteins in membranes database.
Bioinformatics, 22: 623-625 (2006)


Proneth B, Xiang Z, Pogozheva ID, Litherland SA, Gorbatyuk OS, Shaw AM, Millard WJ, Mosberg HI, Haskell-Luevano C
Molecular mechanism of the constitutive activation of the L250Q human melanocortin-4 receptor polymorphism
Chem. Biol. Drug. Des., 67: 215-229 (2006)


Jameson EE, Roof RA, Whorton MR, Mosberg HI, Sunahara RK, Neubig RR Kennedy RT
Real-time detection of basal and stimulated G protein GTPase activity using fluorescent GTP analogues.
J Biol Chem., 280: 7712-7719 (2005)


Pogozheva ID, Przydzial MJ, Mosberg HI
Homology modeling of opioid receptor-ligand complexes using experimental constraints.
AAPS J., 7: E434-E448 (2005)


Przydzial MJ, Pogozheva ID, Ho JC, Tharp TA, Drankhan KE, Sawyer E, Traynor JR, Mosberg HI
Design of high affinity cyclic pentapeptide ligands for kappa-opioid receptors.
J. Pept. Res., 66: 255-262 (2005)


Przydzial MJ, Pogozheva ID, Bosse KE, Andrews SM, Tod A, Tharp TA, Traynor JR, Mosberg HI
Roles of residues 3 and 4 in cyclic tetrapeptide ligand recognition by the kappa- opioid receptor
J. Pept. Res., 65: 333-342 (2005)


Pogozheva ID, Chai B-X, Lomize AL, Fong TM, Weinberg DH, Nargund RH, Mulholland MW, Gantz I, Mosberg HI
Interactions of human melanocortin receptor-4 with small-molecule agonists.
Biochemistry, 44: 11329-11341 (2005)


Chai B-X, Pogozheva ID, Lai Y-M, Li J-Y, Neubig RR, Mosberg HI, Gantz I
Receptor-antagonist interactions in the complexes of agouti protein and agouti-related protein with human melanocortin 1 and 4 receptors.
Biochemistry, 44: 3418-3431 (2005)


Fowler CB, Pogozheva ID, Lomize AL, LeVine H, Mosberg HI
Complex of active mu-opioid receptor with cyclic peptide agonist modeled from experimental constraints.
Biochemistry, 43: 15796-15810 (2004)


Lomize AL, Pogozheva ID, Mosberg HI
Quantification of helix-helix binding affinities in micelles and lipid bilayers.
Protein Sci., 13: 2600-2612 (2004)


Jin Y, Zhong H, Omnaas JR, Neubig RR, Mosberg HI
Structure-based design, synthesis, and activity of peptide inhibitors of RGS4 GAP activity.
Methods Enzymol., 389: 266-277 (2004)


Jin Y, Zhong H, Omnaas JR, Neubig RR, Mosberg HI
Structure-based design, synthesis, and pharmacologic evaluation of peptide RGS4 inhibitors.
J. Pept. Res., 63: 141-146 (2004)


Fowler CB, Pogozheva ID, LeVine H 3rd, Mosberg HI.
Refinement of a homology model of the mu-opioid receptor using distance constraints from intrinsic and engineered zinc-binding sites.
Biochemistry., 43: 8700-8710 (2004)


Vig BS, Lorenzi PJ, Mittal S, Landowski CP, Shin HC, Mosberg HI, Hilfinger JM, Amidon GL
Amino acid ester prodrugs of floxuridine: synthesis and effects of structure, stereochemistry, and site of esterification on the rate of hydrolysis.
Pharm. Res., 20: 1381-1388 (2003)


Mosberg HI, Fowler CB
Development and validation of opioid ligand-receptor interaction models: The structural basis of mu vs. delta selectivity
J. Peptide Res., 60: 329-332 (2002)


Hicks ME, Gomez-Flores R, Wang C, Mosberg HI, Weber RJ
Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions.
Life Sci., 68: 2685-2694 (2001)


McFadyen IJ, Ho JC, Mosberg HI, Traynor JR
Modifications of the cyclic mu receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]NH2 (Et): effects on opioid receptor binding and activation.
J. Pept. Res., 55: 255-261 (2000)


McFadyen IJ, Sobczyk-Kojiro K, Schaefer MJ, Ho JC, Omnaas JR, Mosberg HI, Traynor JR
Tetrapeptide derivatives of [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) lacking an N-terminal tyrosine residue are agonists at the mu-opioid receptor.
Pharmacol. Exp. Ther., 295: 960-966 (2000)


Mosberg HI
Complementarity of delta opioid ligand pharmacophore and receptor models.
Biopolymers, 51: 426-39 (1999)


Lomize AL, Pogozheva ID, Mosberg HI
Prediction of protein structure: The problem of fold multiplicity.
Proteins, 37: 199-203 (1999)


Butelman ER, Ko MC, Sobczyk-Kojiro K, Mosberg HI, Van Bemmel B, Zernig G, Woods JH
kappa-Opioid receptor binding populations in rhesus monkey brain: relationship to an assay of thermal antinociception.
J. Pharmacol. Exp. Ther., 285: 595-601 (1998)


Pogozheva ID, Lomize AL, Mosberg HI
Opioid receptor three-dimensional structures from distance geometry calculations with hydrogen bonding constraints.
Biophys. J., 75: 612-634 (1998)


Mosberg HI, Ho JC, Sobczyk-Kojiro K
A high affinity, mu-opioid receptor-selective enkephalin analogue lacking an N-terminal tyrosine.
Bioorg. Med. Chem. Lett., 8: 2681-2684 (1998)


Wang C, McFadyen IJ, Traynor JR, Mosberg HI
Design of a high affinity peptidomimetic opioid agonist from peptide pharmacophore models.
Bioorg. Med. Chem. Lett., 8: 2685-2688 (1998)


Pogozheva ID, Lomize AL, Mosberg HI
The transmembrane 7-alpha-bundle of rhodopsin: distance geometry calculations with hydrogen bonding constraints.
Biophys. J., 72: 1963-1985 (1997)


Lomize AL, Mosberg HI
Thermodynamic model of secondary structure for alpha-helical peptides and proteins.
Biopolymers., 42: 239-269 (1997)


Mosberg HI, Dua RK, Pogozheva ID, Lomize AL
Development of a model for the delta-opioid receptor pharmacophore. 4. Residue 3dehydrophenylalanine analogues of Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) confirmrequired gauche orientation of aromatic side chain.
Biopolymers, 39: 287-296 (1996)


Lomize AL, Pogozheva ID, Mosberg HI
Development of a model for the delta-opioid receptor pharmacophore: 3. Comparison of the cyclic tetrapeptide, Tyr-c[D-Cys-Phe-D-Pen]OH with other conformationally constrained delta-receptor selective ligands.
Biopolymers., 38: 221-234 (1996)


Mosberg HI, Lomize AL, Wang C, Kroona H, Heyl DL, Sobczyk-Kojiro K, Ma W, Mousigian C, Porreca F
Development of a model for the delta opioid receptor pharmacophore. 1. Conformationally restricted Tyr1 replacements in the cyclic delta receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13).
J. Med. Chem., 37: 4371-4383 (1994)


Mosberg HI, Omnaas JR, Lomize AL, Heyl DL, Nordan I, Mousigian C, Davis P, Porreca F
Development of a model for the delta opioid receptor pharmacophore. 2. Conformationally restricted Phe3 replacements in the cyclic delta receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13).
J. Med. Chem., 37: 4384-4391 (1994)


People People
Henry I. Mosberg
Andrei L.Lomize
Irina D.Pogozheva
Katarzyna Sobczyk-Kojiro
Jessica Anand
Anthony F. Nastase
Sean P. Henry
Deanna Montgomery
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